The broad and long-term objective of this project is to amplify the effectiveness of vaccines without the use of chemical or biological adjuvants. We will address this objective by demonstrating the feasibility for small laser- based devices to enhance responses to intradermal vaccination. A number of investigators have shown that a promising new way to make vaccines work better is to treat the skin with a brief exposure to a non-harmful laser light and then introduce the vaccine at that skin site. This approach can result in better vaccine responses without the need for chemical adjuvants. Until now, these responses have been generated using large and relatively expensive bench top devices. Recently, low-power, near-infrared (NIR) laser light has also been shown to significantly enhancing vaccine responses. This would make it possible to use small, low-cost NIR laser systems to enhance vaccines that would be practical in the clinical setting. There are currently no such portable devices designed to deliver vaccine-enhancing treatments. Therefore, the objectives of this project are 1) to complete a prototype handheld laser that can replicate the beam parameters of a larger laser system that has shown the ability to induce significant enhancement of immune responses to intradermal vaccines, and 2) to demonstrate that this small laser can produce equivalent immune responses to the larger laser in an established mouse vaccination model. This project, if successful, will open the door for greater testing of the laser based adjuvant with a variety of vaccines, and will form the foundation for development of clinical-ready devices. For this project, a set of prototype handheld device will be created using an existing handheld laser design. One device will use a 1064 nm diode and the other a 1300 nm diode (the 1300 nm device will serve as a negative control system). These devices will be built using standard fabrication processes and bench tested to show their emission profile is similar to that which has been described as enhancing vaccine responses. Once these prototypes are built and bench-tested, they will be then be tested side by side with the larger laser systems already shown to enhance vaccine responses. Using an established mouse vaccine model, the small laser systems will first be tested to show the treatment doses are non-harmful and non-damaging to the skin. Following this, their ability to produce equivalent immune responses to an influenza vaccination will be tested, including protection against a lethal challenge with influenza.